Review
Pharmacology of antidepressants

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Presently in the United States, 21 compounds have been approved by the Food and Drug Administration as antidepressants. Two additional drugs marketed outside the United States as antidepressants have been approved for obsessive-compulsive disorder. Nearly one half of all these compounds became available within the past 12 years, whereas the first antidepressant was available more than 40 years ago. After the clinical aspects of depression are introduced in this article, the pharmacology of the newer generation drugs is reviewed in relationship to the older compounds. The information in this review will help clinicians treat acute depression with pharmacological agents.

Section snippets

DIAGNOSIS OF DEPRESSION AND ITS PREVALENCE

Despite extensive research to find a diagnostic test, the diagnosis of depression remains clinical. The criteria for the diagnosis of major depression5 are the core signs and symptoms, including depressed mood, diminished pleasure or interest in activities, pronounced change in appetite or weight, alterations in sleep (insomnia or hypersomnia), psychomotor agitation or retardation, fatigue or loss of energy, inability to concentrate, indecisiveness, and thoughts of death, dying, or suicide.

A

PHARMACOTHERAPY FOR DEPRESSION

Antidepressant drugs are the mainstay for the treatment of depression. Usually, antidepressants are given in combination with some form of limited supportive psychotherapy. For mild depression, psychotherapy alone may be of use. However, evidence is accumulating that the combination of antidepressant treatment and some form of psychotherapy may be superior to either treatment alone, especially for more severe and recurrent depression.25, 26, 27

Over the past decade, the so-called tricyclic

CLASSIFICATION OF AVAILABLE ANTIDEPRESSANTS

When fewer antidepressant compounds were available, the drugs were classified either as tricyclic antidepressants or as monoamine oxidase inhibitors (MAOIs), a classification that mixes a structural criterion with a functional one. At present, a broad range of structures make up the antidepressant pharmacopoeia, but there are only a few known functional (possibly therapeutic) effects of these compounds. Therefore, a functional classification of antidepressants is more useful than a structural

Onset of Activity

Practicing clinicians know that the mood-elevating effect of antidepressant medication usually begins about 1 to 2 weeks after initiation of treatment. The clinical rule of thumb is that a patient must be treated with an adequate dosage for at least 6 weeks before the clinician considers changing the treatment. However, the synaptic effects of these drugs occur within hours after the patient ingests the drug.31 Because many of the early adverse effects have the same time course as the early

CONCLUSION: THE FUTURE, PAST, AND PRESENT

What might the future bring with respect to the pharmacological treatment of depression in the United States? Compounds that block transporters are still under development. For example, reboxetine, a compound selective for the norepinephrine transporter, may be marketed in the United States within the next few years, several years after the marketing of this compound outside the United States. Drugs that potently block more than 1 transporter are also under development. An example of this class

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    In the recent past, I have given lectures sponsored by GlaxoSmithKline, Janssen Pharmaceutica, Organon, and Pfizer. Also, I received a grant from Pharmacia.

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